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Nanometer nucleic acid guide medicine, and preparation method and application thereof

A nucleic acid drug and drug technology, used in drug combinations, pharmaceutical formulations, anti-tumor drugs, etc., can solve the problems of inability to effectively reach the lesions, reduce the clinical application effect, and limit the effect of nucleic acid drugs.

Inactive Publication Date: 2012-07-25
东莞市麦亘生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, microRNA is easily degraded after entering the body, which greatly reduces its clinical application effect
[0005] At present, nucleic acid drugs are mostly in the research stage for the treatment of cancer. Simple oligonucleotides enter the human body and are completely decomposed by blood nucleases in the body in a short period of time (a few minutes to ten minutes), and cannot effectively reach the lesion. Due to molecular weight Small and easy to excrete with urine through the kidneys, non-specific drug metabolism greatly limits the effect of nucleic acid drugs

Method used

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  • Nanometer nucleic acid guide medicine, and preparation method and application thereof
  • Nanometer nucleic acid guide medicine, and preparation method and application thereof
  • Nanometer nucleic acid guide medicine, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0073] The synthesis of embodiment 1, C32

[0074] 1. Melt 400ul of 5-amino-1-pentanol in a 40°C water bath;

[0075] 2. Use a pipette to absorb 356ul of 5-amino-1-pentanol and 651ul of 1,4-butanediol diacrylate, 5-amino-1-pentanol and 1,4-butanediol diacrylate The molar ratio is 1.2:1.0, mix thoroughly and put into the centrifuge tube;

[0076] 3. Let it react at 94°C for 24 hours, and polymerize into C32 under suitable conditions;

[0077] 4. Dissolve the C32 completed in the above reaction with DMSO to prepare a 10ml solution (concentration is 100mg / ml);

[0078] 5. Sterile filter the solution with a 0.22um filter membrane, and distribute it in ten small centrifuge tubes of 1.5ml;

[0079] 6. Store at -20°C for later use.

Embodiment 2

[0080] Embodiment 2, MicroRNA

[0081] See Table 1 for valid nucleic acid chains. Including: Mir-34, miR-122, miR-125, miR-130a, miR-150, miR-199, miR-200 and let-7 family members.

[0082] Table 1

[0083]

Embodiment 3

[0084] Embodiment 3, the preparation of the nucleic acid medicine that comprises targeting peptide

[0085] Targeting polypeptides used (see Lee, et al, cancer research 2007:67(22), Jia et al Cancer Letters 247(2007) 234-242; Du et al, Mol Cancer Res.2010; 8(2):135-144 ) see Table 2.

[0086] Table 2

[0087] Peptide name

SEQ ID NO:

amino acid sequence

SP5-52

11

SVSVGMKPSPRP

12

AWYPLPP

13

AQYPLPP

A54

14

AGKGTPSLETTP

[0088] (a) C32-A54 targeting peptide modification

[0089]Add A54 (AGKGTPSLETTP) with a molar ratio of 1.0: 2.4 (C32: A54) in 5 milliliters of DMSO solution containing 1.9 grams of C32 to carry out esterification reaction. The optimum process condition for the synthesis reaction is: the molar ratio of C32 and A54 is 1.0 : 2.4, Catalyst SO 4 2- / SiO 2 The dosage is 0.19g, the reaction temperature is 60°C, and the reaction time is 4h. At this time, the esterification yield i...

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Abstract

The invention relates to nanometer nucleic acid guide medicine, and a preparation method and application thereof. The nanometer nucleic acid guide medicine uses nanometer materials as carriers, wherein the nanometer materials comprise guide materials and nucleic acid medicine, and in addition, hydrophilic compounds are modified on the surface of the compound. The nanometer nucleic acid guide medicine has good target specificity and has low nonspecific absorption on plasma protein, vessel wall and other tissues.

Description

technical field [0001] The invention belongs to the field of biotechnology; more specifically, the invention relates to a nano-nucleic acid-guided drug and its preparation method and application. Background technique [0002] In recent years, molecular targeted drugs have shown their value in tumor therapy. In this field, the treatment targeting signal transduction of cell receptors, genes, regulatory molecules, etc. is called "targeted therapy". [0003] Targeted therapy is a trend in tumor treatment, and its side effects are lower than those of cytotoxic drugs. Therefore, although the efficacy of targeted drugs is not obvious at present, it has brought hope to cancer patients and provided new ideas and methods for cancer treatment. [0004] The biggest problem in the clinical application of many nucleic acid drugs is that they are easily degraded in the body and difficult to reach the target site. This is an insurmountable technical problem in this field, which greatly li...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K48/00A61K47/48A61P35/00A61P1/16A61P11/00A61K47/60
Inventor 李相鲁赵念玺张严冬邹水洋
Owner 东莞市麦亘生物科技有限公司